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Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation

Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthi...

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Autores principales: Chen, Guangrui, Li, Jian, Liu, Huimeng, Zhou, Huiyu, Liu, Mingqiu, Liang, Di, Meng, Zhiyun, Gan, Hui, Wu, Zhuona, Zhu, Xiaoxia, Han, Peng, Liu, Taoyun, Gu, Ruolan, Liu, Shuchen, Dou, Guifang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864377/
https://www.ncbi.nlm.nih.gov/pubmed/36677811
http://dx.doi.org/10.3390/molecules28020753
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author Chen, Guangrui
Li, Jian
Liu, Huimeng
Zhou, Huiyu
Liu, Mingqiu
Liang, Di
Meng, Zhiyun
Gan, Hui
Wu, Zhuona
Zhu, Xiaoxia
Han, Peng
Liu, Taoyun
Gu, Ruolan
Liu, Shuchen
Dou, Guifang
author_facet Chen, Guangrui
Li, Jian
Liu, Huimeng
Zhou, Huiyu
Liu, Mingqiu
Liang, Di
Meng, Zhiyun
Gan, Hui
Wu, Zhuona
Zhu, Xiaoxia
Han, Peng
Liu, Taoyun
Gu, Ruolan
Liu, Shuchen
Dou, Guifang
author_sort Chen, Guangrui
collection PubMed
description Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthine (CEP), in a cell culture model of transforming growth factor-β1 (TGF-β1) and bleomycin (BLM)-induced pulmonary fibrosis rat models both in vitro and in vivo. In this study, CEP and pirfenidone (PFD) suppressed BLM-induced lung tissue inflammation, proliferation of blue collagen fibers, and damage to lung structures in vivo. Furthermore, we also found increased collagen deposition marked by α-smooth muscle actin (α-SMA) and Collagen Type I Alpha 1 (COL1A1), which was significantly alleviated by the addition of PFD and CEP. Moreover, we elucidated the underlying mechanism of CEP against PF in vitro. Various assays confirmed that CEP reduced the viability and migration and promoted apoptosis of myofibroblasts. The expression levels of myofibroblast markers, including COL1A1, vimentin, α-SMA, and Matrix Metallopeptidase 2 (MMP2), were also suppressed by CEP. Simultaneously, CEP significantly suppressed the elevated Phospho-NF-κB p65 (p-p65)/NF-κB p65 (p65) ratio, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels, and elevated inhibitor of NF-κB Alpha (IκBα) degradation and reversed the progression of PF. Hence, our study demonstrated that CEP prevented myofibroblast activation and treated BLM-induced pulmonary fibrosis in a dose-dependent manner by regulating nuclear factor kappa-B (NF-κB)/ NLRP3 signaling, thereby suggesting that CEP has potential clinical application in pulmonary fibrosis in the future.
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spelling pubmed-98643772023-01-22 Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation Chen, Guangrui Li, Jian Liu, Huimeng Zhou, Huiyu Liu, Mingqiu Liang, Di Meng, Zhiyun Gan, Hui Wu, Zhuona Zhu, Xiaoxia Han, Peng Liu, Taoyun Gu, Ruolan Liu, Shuchen Dou, Guifang Molecules Article Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthine (CEP), in a cell culture model of transforming growth factor-β1 (TGF-β1) and bleomycin (BLM)-induced pulmonary fibrosis rat models both in vitro and in vivo. In this study, CEP and pirfenidone (PFD) suppressed BLM-induced lung tissue inflammation, proliferation of blue collagen fibers, and damage to lung structures in vivo. Furthermore, we also found increased collagen deposition marked by α-smooth muscle actin (α-SMA) and Collagen Type I Alpha 1 (COL1A1), which was significantly alleviated by the addition of PFD and CEP. Moreover, we elucidated the underlying mechanism of CEP against PF in vitro. Various assays confirmed that CEP reduced the viability and migration and promoted apoptosis of myofibroblasts. The expression levels of myofibroblast markers, including COL1A1, vimentin, α-SMA, and Matrix Metallopeptidase 2 (MMP2), were also suppressed by CEP. Simultaneously, CEP significantly suppressed the elevated Phospho-NF-κB p65 (p-p65)/NF-κB p65 (p65) ratio, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels, and elevated inhibitor of NF-κB Alpha (IκBα) degradation and reversed the progression of PF. Hence, our study demonstrated that CEP prevented myofibroblast activation and treated BLM-induced pulmonary fibrosis in a dose-dependent manner by regulating nuclear factor kappa-B (NF-κB)/ NLRP3 signaling, thereby suggesting that CEP has potential clinical application in pulmonary fibrosis in the future. MDPI 2023-01-11 /pmc/articles/PMC9864377/ /pubmed/36677811 http://dx.doi.org/10.3390/molecules28020753 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Guangrui
Li, Jian
Liu, Huimeng
Zhou, Huiyu
Liu, Mingqiu
Liang, Di
Meng, Zhiyun
Gan, Hui
Wu, Zhuona
Zhu, Xiaoxia
Han, Peng
Liu, Taoyun
Gu, Ruolan
Liu, Shuchen
Dou, Guifang
Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation
title Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation
title_full Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation
title_fullStr Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation
title_full_unstemmed Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation
title_short Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation
title_sort cepharanthine ameliorates pulmonary fibrosis by inhibiting the nf-κb/nlrp3 pathway, fibroblast-to-myofibroblast transition and inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864377/
https://www.ncbi.nlm.nih.gov/pubmed/36677811
http://dx.doi.org/10.3390/molecules28020753
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